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Importance: The optimal dose and duration of oral amoxicillin for children with community-acquired pneumonia (CAP) are unclear.Objective: To determine whether lower-dose amoxicillin is noninferior to higher dose and whether 3-day treatment is noninferior to 7 days.Design, Setting, and Participants: Multicenter, randomized, 2 × 2 factorial noninferiority trial enrolling 824 children, aged 6 months and older, with clinically diagnosed CAP, treated with amoxicillin on discharge from emergency departments and inpatient wards of 28 hospitals in the UK and 1 in Ireland between February 2017 and April 2019, with last trial visit on May 21, 2019.Interventions: Children were randomized 1:1 to receive oral amoxicillin at a lower dose (35-50 mg/kg/d; n = 410) or higher dose (70-90 mg/kg/d; n = 404), for a shorter duration (3 days; n = 413) or a longer duration (7 days; n = 401).Main Outcomes and Measures: The primary outcome was clinically indicated antibiotic re-treatment for respiratory infection within 28 days after randomization. The noninferiority margin was 8%. Secondary outcomes included severity/duration of 9 parent-reported CAP symptoms, 3 antibiotic-related adverse events, and phenotypic resistance in colonizing Streptococcus pneumoniae isolates.Results: Of 824 participants randomized into 1 of the 4 groups, 814 received at least 1 dose of trial medication (median [IQR] age, 2.5 years [1.6-2.7]; 421 [52%] males and 393 [48%] females), and the primary outcome was available for 789 (97%). For lower vs higher dose, the primary outcome occurred in 12.6% with lower dose vs 12.4% with higher dose (difference, 0.2% [1-sided 95% CI -∞ to 4.0%]), and in 12.5% with 3-day treatment vs 12.5% with 7-day treatment (difference, 0.1% [1-sided 95% CI -∞ to 3.9]). Both groups demonstrated noninferiority with no significant interaction between dose and duration (P = .63). Of the 14 prespecified secondary end points, the only significant differences were 3-day vs 7-day treatment for cough duration (median 12 days vs 10 days; hazard ratio [HR], 1.2 [95% CI, 1.0 to 1.4]; P = .04) and sleep disturbed by cough (median, 4 days vs 4 days; HR, 1.2 [95% CI, 1.0 to 1.4]; P = .03). Among the subgroup of children with severe CAP, the primary end point occurred in 17.3% of lower-dose recipients vs 13.5% of higher-dose recipients (difference, 3.8% [1-sided 95% CI, -∞ to10%]; P value for interaction = .18) and in 16.0% with 3-day treatment vs 14.8% with 7-day treatment (difference, 1.2% [1-sided 95% CI, -∞ to 7.4%]; P value for interaction = .73).Conclusions and Relevance: Among children with CAP discharged from an emergency department or hospital ward (within 48 hours), lower-dose outpatient oral amoxicillin was noninferior to higher dose, and 3-day duration was noninferior to 7 days, with regard to need for antibiotic re-treatment. However, disease severity, treatment setting, prior antibiotics received, and acceptability of the noninferiority margin require consideration when interpreting the findings.Trial Registration: ISRCTN Identifier: ISRCTN76888927. [ABSTRACT FROM AUTHOR]

Objective: To describe the epidemiology and aetiology of paediatric traumatic cardiac arrest (TCA) in England and Wales.Design: Population-based analysis of the UK Trauma Audit and Research Network (TARN) database.Patients and Setting: All paediatric and adolescent patients with TCA recorded on the TARN database for a 10-year period (2006-2015).Measures: Patient demographics, Injury Severity Score (ISS), location of TCA ('prehospital only', 'in-hospital only' or 'both'), interventions performed and outcome.Results: 21 710 paediatric patients were included in the database; 129 (0.6%) sustained TCA meeting study inclusion criteria. The majority, 103 (79.8%), had a prehospital TCA. 62.8% were male, with a median age of 11.7 (3.4-16.6) years, and a median ISS of 34 (25-45). 110 (85.3%) had blunt injuries, with road-traffic collision the most common mechanism (n=73, 56.6%). 123 (95.3%) had severe haemorrhage and/or traumatic brain injury. Overall 30-day survival was 5.4% ((95% CI 2.6 to 10.8), n=7). 'Pre-hospital only' TCA was associated with significantly higher survival (n=6) than those with TCA in both 'pre-hospital and in-hospital' (n=1)-13.0% (95% CI 6.1% to 25.7%) and 1.2% (95% CI 0.1% to 6.4%), respectively, p<0.05. The greatest survival (n=6, 10.3% (95% CI 4.8% to 20.8%)) was observed in those transported to a paediatric major trauma centre (MTC) (defined as either a paediatric-only MTC or combined adult-paediatric MTC).Conclusions: Survival is possible from the resuscitation of children in TCA, with overall survival comparable to that reported in adults. The highest survival was observed in those with a pre-hospital only TCA, and those who were transported to an MTC. Early identification and aggressive management of paediatric TCA is advocated. [ABSTRACT FROM AUTHOR]

Aim: Penetrating head injuries (pHIs) are associated with high morbidity and mortality. Data on pHIs in children outside North America are limited. We describe the mechanism of injuries, neuroimaging findings, neurosurgery and mortality for pHIs in Australia and New Zealand.Methods: This was a planned secondary analysis of a prospective observational study of children <18 years who presented with a head injury of any severity at any of 10 predominantly paediatric Australian/New Zealand emergency departments (EDs) between 2011 and 2014. We reviewed all cases where clinicians had clinically suspected pHI as well as all cases of clinically important traumatic brain injuries (death, neurosurgery, intubation >24 h, admission >2 days and abnormal computed tomography).Results: Of 20 137 evaluable patients with a head injury, 21 (0.1%) were identified to have sustained a pHI. All injuries were of non-intentional nature, and there were no gunshot wounds. The mechanisms of injuries varied from falls, animal attack, motor vehicle crashes and impact with objects. Mean Glasgow Coma Scale on ED arrival was 10; 10 (48%) had a history of loss of consciousness, and 7 (33%) children were intubated pre-hospital or in the ED. Fourteen (67%) children underwent neurosurgery, two (10%) craniofacial surgery, and five (24%) were treated conservatively; four (19%) patients died.Conclusions: Paediatric pHIs are very rare in EDs in Australia and New Zealand but are associated with high morbidity and mortality. The absence of firearm-related injuries compared to North America is striking and may reflect Australian and New Zealand firearm regulations. [ABSTRACT FROM AUTHOR]

Background: Convulsive status epilepticus (CSE) is the most common life-threatening neurological emergency in childhood. These children are also at risk of significant morbidity, with acute and chronic impact on the family and the health and social care systems. The current recommended first-choice, second-line treatment in children aged 6 months and above is intravenous phenytoin (fosphenytoin in the USA), although there is a lack of evidence for its use and it is associated with significant side effects. Emerging evidence suggests that intravenous levetiracetam may be effective as a second-line agent for CSE, and fewer adverse effects have been described. This trial therefore aims to determine whether intravenous phenytoin or levetiracetam is more effective, and safer, in treating childhood CSE.Methods/design: This is a phase IV, multi-centre, parallel group, randomised controlled, open-label trial. Following treatment for CSE with first-line treatment, children with ongoing seizures are randomised to receive either phenytoin (20 mg/kg, maximum 2 g) or levetiracetam (40 mg/kg, maximum 2.5 g) intravenously. The primary outcome measure is the cessation of all visible signs of CSE as determined by the treating clinician. Secondary outcome measures include the need for further anti-seizure medications or rapid sequence induction for ongoing CSE, admission to critical care areas, and serious adverse reactions. Patients are recruited without prior consent, with deferred consent sought at an appropriate time for the family. The primary analysis will be by intention-to-treat. The primary outcome is a time to event outcome and a sample size of 140 participants in each group will have 80% power to detect an increase in CSE cessation rates from 60% to 75%. Our total sample size of 308 randomised and treated participants will allow for 10% loss to follow-up.Discussion: This clinical trial will determine whether phenytoin or levetiracetam is more effective as an intravenous second-line agent for CSE, and provide evidence for management recommendations. In addition, this trial will also provide data on which of these therapies is safer in this setting.Trial Registration: ISRCTN identifier, ISRCTN22567894 . Registered on 27 August 2015 EudraCT identifier, 2014-002188-13 . Registered on 21 May 2014 NIHR HTA Grant: 12/127/134. [ABSTRACT FROM AUTHOR]

Background: No previous studies have validated current clinical practice guidelines for the management of non-blanching rashes in children who have received meningococcal B and C vaccinations. The aim of this study was to evaluate the performance of existing clinical practice guidelines in the diagnosis of invasive meningococcal disease in children presenting with a fever and non-blanching rash in the UK.Methods: The Petechiae in Children (PiC) study was a prospective, multicentre cohort study involving children (aged <18 years) presenting to 37 paediatric emergency departments in the UK with a fever (≥38°C) and a new-onset non-blanching rash or features suggestive of meningococcal infection. Children with pre-existing haematological conditions (ie, haematological malignancy, idiopathic thrombocytopenic purpura, or coagulopathy) or an existing diagnosis of Henoch-Schonlein purpura were excluded. Invasive meningococcal disease was confirmed by positive culture or a quantitative PCR test for Neisseria meningitidis from either blood or cerebrospinal fluid samples. The primary outcome was the performance of six tailored clinical practice guidelines from participating centres (London, Nottingham, Newcastle-Birmingham-Liverpool, Glasgow, Chester, and Bristol) and two clinical practice guidelines from the National Institutes for Health and Care Excellence (NICE; CG102 and NG51) in identifying children with invasive meningococcal disease, assessed by the sensitivity and specificity of each clinical practice guideline. This study is registered with ClinicalTrials.gov, NCT03378258.Findings: Between Nov 9, 2017, and June 30, 2019, 1513 patients were screened, of whom 1329 were eligible and were included in the analysis. The median age of patients was 24 months (IQR 12-48). 1137 (86%) of 1329 patients had a blood test and 596 (45%) received parenteral antibiotics. 19 (1%) patients had confirmed meningococcal disease. All eight clinical practice guidelines had a sensitivity of 1·00 (95% CI 0·82-1·00) for identifying meningococcal disease. The specificities of NICE guidelines CG102 (0·01 [95% CI 0·01-0·02]) and NG51 (0·00 [0·00-0·00]) for identifying meningococcal disease were significantly lower than that of tailored clinical practice guidelines (p<0·0001). The best performing clinical practice guidelines for identifying meningococcal disease were the London (specificity 0·36 [0·34-0·39]) and Nottingham (0·34 [0·32-0·37]) clinical practice guidelines.Interpretation: Invasive meningococcal disease is a rare cause of non-blanching rashes in children presenting to the emergency department in the UK. Current NICE guidelines perform poorly when compared with tailored clinical practice guidelines. These findings suggest that UK national guidance could be improved by shifting towards a tailored approach.Funding: Public Health Agency. [ABSTRACT FROM AUTHOR]

Background: Clinical decision rules can help to determine the need for CT imaging in children with head injuries. We aimed to validate three clinical decision rules (PECARN, CATCH, and CHALICE) in a large sample of children.Methods: In this prospective observational study, we included children and adolescents (aged <18 years) with head injuries of any severity who presented to the emergency departments of ten Australian and New Zealand hospitals. We assessed the diagnostic accuracy of PECARN (stratified into children aged <2 years and ≥2 years), CATCH, and CHALICE in predicting each rule-specific outcome measure (clinically important traumatic brain injury [TBI], need for neurological intervention, and clinically significant intracranial injury, respectively). For each calculation we used rule-specific predictor variables in populations that satisfied inclusion and exclusion criteria for each rule (validation cohort). In a secondary analysis, we compiled a comparison cohort of patients with mild head injuries (Glasgow Coma Scale score 13-15) and calculated accuracy using rule-specific predictor variables for the standardised outcome of clinically important TBI. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614000463673.Findings: Between April 11, 2011, and Nov 30, 2014, we analysed 20 137 children and adolescents attending with head injuries. CTs were obtained for 2106 (10%) patients, 4544 (23%) were admitted, 83 (<1%) underwent neurosurgery, and 15 (<1%) died. PECARN was applicable for 4011 (75%) of 5374 patients younger than 2 years and 11 152 (76%) of 14 763 patients aged 2 years and older. CATCH was applicable for 4957 (25%) patients and CHALICE for 20 029 (99%). The highest point validation sensitivities were shown for PECARN in children younger than 2 years (100·0%, 95% CI 90·7-100·0; 38 patients identified of 38 with outcome [38/38]) and PECARN in children 2 years and older (99·0%, 94·4-100·0; 97/98), followed by CATCH (high-risk predictors only; 95·2%; 76·2-99·9; 20/21; medium-risk and high-risk predictors 88·7%; 82·2-93·4; 125/141) and CHALICE (92·3%, 89·2-94·7; 370/401). In the comparison cohort of 18 913 patients with mild injuries, sensitivities for clinically important TBI were similar. Negative predictive values in both analyses were higher than 99% for all rules.Interpretation: The sensitivities of three clinical decision rules for head injuries in children were high when used as designed. The findings are an important starting point for clinicians considering the introduction of one of the rules.Funding: National Health and Medical Research Council, Emergency Medicine Foundation, Perpetual Philanthropic Services, WA Health Targeted Research Funds, Townsville Hospital Private Practice Fund, Auckland Medical Research Foundation, A + Trust. [ABSTRACT FROM AUTHOR]